7. European Journal of Cardio-Thoracic Surgery 25 (2004) 523-529
Intracellular vacuoles
Interstitial & mitocondrial edema
Dilatation in endoplasmic reticulum & Golgi
Chromatin desintegration in the nucleus
2h 8h 24h
G5
8. Weight
Crit Care Med 2005;33:1077-83
0 500 1000 1500 2000
Time (sec)
30.0
25.0
20.0
15.0
10.0
5.0
0.0
Weight (gr)
MMaassssiivvee BBrraaiinn
IInnjjuurryy
CCoonnttrrooll
12. JAMA. 2010;304(23):2620-2627
Potential donors were randomized to conventional
ventilatory strategy: VT 10-12 mL/kg PBW & PEEP
3-5 cmH2O or the protective ventilatory strategy: VT
6-8 mL/kg PBW & PEEP 8-10 cmH2O.
Use of a lung protective strategy in potential organ
donors with brain death increased the number of
eligible and harvested lungs compared with a
conventional strategy.
14. Brain Areas of Interest in Coronal Section
CeA
PVP
CX
Rts CX
CX
Hippocampus
RtsCX: Retrosplenial Cortex, CeA: Central Amygdala
Cortex, Hippocampus, PVP: Paraventricular Thalamic nucleus,
PVN: Paraventricular Hypothalamic Nucleus
15. Basal
Spontaneous
Breathing
Low VT
High VT
Central Amygdala
Quilez M et al. Crit Care. 2011;15(3):R124
Functions:
- motivated behaviours
- emotional states
- housekeeping activities
Injury:
- cognitive impaiments
16. Retrosplenial Cortex
Quilez M et al. Crit Care. 2011;15(3):R124
Basal
Spontaneous
Breathing
Low VT
High VT
Functions:
- spatial memory
- learning
Injury:
- memory deficits
17. Thalamus
Quilez M et al. Crit Care. 2011;15(3):R124
Basal
Spontaneous
Breathing
Low VT
High VT
Functions:
-Interpretation of
sensory information
Injury:
- good or bad ???
18. Am J Respir Crit Care Med Vol 183. pp 471–482, 2011
Effect of vagotomy on high VT ventilation-induced ALI in mice
BALF
Lung
Tissue
19. Am J Respir Crit Care Med Vol 183. pp 471–482, 2011
Effect of administration of the vagus mimetic drug, semapimod,
on VILI (VT 20 ml/kg, PEEP 0)
In experimental VILI, vagotomy exacerbated
while vagus stimulation attenuates lung injury
in rats ventilated with either high or low
volume strategies. Treatment of both mice and
rats with the vagus mimetic drug, semapimod,
resulted BALF
in decreased lung injury.
21. Experimental model of VAP (72h), induced by
translocation of oropharyngeal pathogens to
the lung
Li Bassi G. Anesthesiology 2014; 120:1205-15
22. Cognitive impairment
Moderate to severe cognitive impairment occur
after critical illness (memory, attention, executive
function) and persist months to years after
hospital discharge
Wilcox ME et al. Crit Care Med. 2013, 41: S81-98
Pandharipande PP et al. N Engl J Med. 2013; 369: 1306-16
Hopkins RO. Crit Care. 2013; 6;17(1):116
Prolonged trendelenburg positioning could
induce neurological complications
Schramm P et al. Anaesthesia. 2014; 69:58-63.
Pandey R, et al. Acta Anaesthesiol Belg 2010; 61:163-6
23. Experimental groups
PEEP
(cmH2O)
I:E Position
0
SR-inv
0.7 5
SR n=7
0.33 0 TL TL
n=7
VM 72h, FiO2 40%, Vt 10 ml/kg
SR
n=3
0.33 SR
24. Microscopical evaluation of Dentate
gyrus in the hippocampal formation
HHiippppooccaammppaall ffoorrmmaattiioonn
Dentate Gyrus
25. Dentate gyrus function
Plays an important role in learning and
memory
Ability to generate new neurons on a
daily basis throughout life. Under normal
conditions, new cells are constantly
generated in the dentate gyrus in the
hippocampus
26. hypereosinophilia caspase-3 TUNEL assay
Dentate gyrus (hippocampal formation)
neurodegeneration (hypereosinophilia)
apoptosis
TUNEL (marker of DNA fragmentation)
Caspase-3 (early marker of apoptosis)
28. Results. Hemodynamics
Mean arterial Pressure
120 * TL vs SR
0 6 12 18 24 30 36 42 48 54 60 66 72
110
100
90
80
70
60
* TL vs SR-inv
Time (hours)
M A P ( m m H g )
Central venous pressure
0 6 12 18 24 30 36 42 48 54 60 66 72
15
10
5
0
Time (hours)
C V P
Pressure
TL vs SR
TL vs SR-inv
Central venous pressure
15
10
5
0
C V P
SR
SR-inv
TL
29. Results: Respiratory variables
Pplateau
0 24 48 72
18
17
16
15
14
13
12
11
10
* SR-inv vs SR
* SR-inv vs TL
Time (hours)
P p l a t ( c m H 2 O )
Crs
0 24 48 72
35
30
25
20
15
* SR-inv vs TL
Time (hours)
C r s ( m l / c m H 2 O )
Pressure
TL vs SR
TL vs SR-inv
Central venous pressure
15
10
5
0
C V P
SR
SR-inv
TL
30. Results. Brain Hemorrhage score
Petequial Cerebral Hemorrhage Score
4 *
SR SR-inv TR
3
2
1
0
*
S C O R E
SR SR-inv TL
31. Results. Dentate gyrus (Hippocampus)
Apoptosis in Dentate Gyrus (Hippocampal formation)
Hypereosinophilic cells (H&E)
SR SR-inv TR
10.0
7.5
5.0
2.5
0.0
*
*
n º p o s i t i v e c e l l s p e r f i e l d
Cleaved Caspase-3
12.5 *
SR SR-inv TR
10.0
7.5
5.0
2.5
0.0
n º p o s i t i v e c e l l s p e r f i e l d
SR SR-inv TL
TUNEL
SR SR-inv TR
10.0
7.5
5.0
2.5
0.0
*
*
n º p o s i t i v e c e l l s p e r f i e l d
Hippocampal ffoorrmmaattiioonn
Dentate Gyrus
SR SR-inv TL SR SR-inv TL
33. Neurophysiologic
Model of
Respiratory Discomfort:
Air Hunger
Work/Effort
Tightness
O’Donnell DE et al
Resp Physiol Neurobiol 2009
34. J Neurophysiol 2002;88:1500-1511
Air Hunger Increases MRI Signal in Insula (Limbic System)
Insula
Insula (Limbic System):
-Perception of dyspnea, hunger, thirst
-Afferents of resp. chemoreceptors
-Stretch receptors project to insula
-Seat of emotions
-Large role in memory
Air hunger may cause severe
psychological trauma
35. Crit Care Med 2011;39:2059-65
45 patients (47%) reported dyspnea (respiratory effort in
seven cases, air hunger in 15, both in 16, and neither
of these in seven).
Dyspneic and nondyspneic patients did not differ in
terms of age, SAPS II or indication for MV.
Dyspnea was significantly associated with anxiety (OR,
8.84; 95%CI, 3.26 –24.0), assistcontrol ventilation (OR,
4.77; 95% CI, 1.60–4.3), and heart rate (OR, 1.33 per 10
beats/min; 95% CI, 1.02–1.75).
36. Hours
Asynchrony
Report
Discomfort
Dyspnea
- Air Hunger
- Work/Effort
- Tightness
Agitation
Risk of Extubation
?
37. Mechanical Ventilation-Induced Reverse-Triggered Breaths
Reverse triggering & Respiratory Entrainment
Stretch receptors & vagal C fibers are responsible for the
Hering-Breuer reflexes
Akoumianaki E et al. Chest 2013;143:927-38.
38. Conclusions:
• Cross-Talk exists between lung and brain
during critical illness.
• Patients with ALI/ARDS & brain injury need
protection and support to both organs.
• Research on this area is in its infancy but this
knowledge can benefit patients, their families
and care providers.
